Evidence map›Paper›PMID 28692575›Full record

ReviewCurrent opinion in hematology2017

Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.

Nabil K Thalji, Rodney M Camire

Open access · greenAbstract readReview
In one paragraph

Review in Current opinion in hematology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 45% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Directed Evolution Methods for Enzyme Engineering.Molecules (Basel, Switzerland) · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Nabil K ThaljiDivision of Hematology, Department of Pediatrics, The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rodney M Camire
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007170 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 1985 to 2022
$54.0M
Structural Correlates of Protease and Cofactor FunctionP01HL074124 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI KRISHNASWAMY, SRIRAM · 2003 to 2013
$17.6M
HEMATOLOGY CLINICAL RESEARCH TRAINING PROGRAMT32HL007439 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LAWRENCE F BRASS, PETER S KLEIN · 1985 to 2026
$17.1M
Mechanisms Regulating Factor V Activation and FunctionR01HL131833 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI CAMIRE, RODNEY M · 2016 to 2018
$946k
Reversal of Direct FXa Inhibitors Using Zymogen-Like Variants of FXaF30HL120487 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THALJI, NABIL · 2013 to 2015
$101k
NHLBI NIH HHS F30 HL120487NHLBI NIH HHS P01 HL074124NHLBI NIH HHS R01 HL131833NHLBI NIH HHS T32 HL007439NIGMS NIH HHS T32 GM007170
6 · The paper itself

Abstract

purpose of reviewNew therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future development prospects. RECENT

findingsUnderlying many procoagulant therapeutic approaches is the rapid generation of thrombin to promote robust clot formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide effective hemostasis to mitigate bleeding in hemophilia and other clinical situations. Over the past decade, we explored the possibility of using zymogen-like factor Xa variants to rapidly improve clot formation for the treatment of bleeding conditions. Compared to the wild-type enzyme, these variants adopt an altered, low activity, conformation which enables them to resist plasma protease inhibitors. However, zymogen-like factor Xa variants are conformationally dynamic and ligands such as its cofactor, factor Va, stabilize the molecule rescuing procoagulant activity. At the site of vascular injury, the variants in the presence of factor Va serve as effective prohemostatic agents. Preclinical data support their use to stop bleeding in a variety of clinical settings. Phase 1 studies suggest that zymogen-like factor Xa is safe and well tolerated, and a phase 1b is ongoing to assess safety in patients with intracerebral hemorrhage. SUMMARY: Zymogen-like factor Xa is a unique prohemostatic agent for the treatment of a range of bleeding conditions.

Indexed as

Hemostatic TechniquesBlood CoagulationClinical Trials, Phase I as TopicEnzyme PrecursorsFactor VaFactor XaHemorrhageHumansEnzyme PrecursorsFactor VaFactor Xa

Identifiers

PMID28692575
PMCPMC5629015
OpenAlexW2733843990

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.